A general strategy to prepare different types of polysaccharide-graft-poly(aspartic acid) as degradable gene carriers

Abstract

Owing to their unique properties such as low cytotoxicity and excellent biocompatibility, poly(aspartic acid) (PAsp) and polysaccharides are good candidates for the development of new biomaterials. In order to construct better gene delivery systems by combining polysaccharides with PAsp, in this work, a general strategy is described for preparing series of polysaccharide-graft-PAsp (including cyclodextrin (CD), dextran (Dex) and chitosan (CS)) gene vectors. Such different polysaccharide-based vectors are compared systematically through a series of experiments including degradability, pDNA condensation capability, cytotoxicity and gene transfection ability. They possess good degradability, which would benefit the release of pDNA from the complexes. They exhibit significantly lower cytotoxicity than the control 'gold-standard' polyethylenimine (PEI, ∼25kDa). More importantly, the gene transfection efficiency of Dex- and CS-based vectors is 12-14-fold higher than CD-based ones. This present study indicates that properly grafting degradable PAsp from polysaccharide backbones is an effective means of producing a new class of degradable biomaterials.

Keywords: Chitosan; Dextran; Gene vectors; Poly(aspartic acid); β-Cyclodextrin.